Multiple hypothalamic sites control the frequency of hippocampal theta rhythm

Abstract

Stimulation of a neural pathway originating in the brainstem reticular formation, with synapses in the medial hypothalamus, activates the hippocampal theta rhythm. The frequency of reticular-elicited theta is determined in the medial supramammillary nucleus (mSuM) completely in anaesthetised rats, but only partially when the animal is awake. We tested other medial hypothalamic sites for their capacity to control theta frequency in awake rats. Blockade of sodium channels (1 microl fast infusion of the local anaesthetic procaine, experiment 1) or increased inhibition by GABA (Chlordiazepoxide [CDP], experiment 2) was found to reduce or increase the frequency of reticular-elicited theta, depending on the precise site of injection, in the region of the dorsomedial hypothalamic nucleus (DMH) and the posterior hypothalamic nucleus (PH). A band of null sites for CDP was located in the region of the ventral border of PH and dorsal border of mSuM. Using 0.5 and 1 microl CDP, and slow infusions (experiment 3), it was found that effective PH sites were also separate from mSuM in the rostrocaudal direction. In experiment 4, the DMH/PH region was mapped with unilateral and bilateral slow infusions of 0.5 microl CDP. CDP significantly reduced frequency in medial (periventricular) and dorsal PH, but not DMH. Bilateral injections appeared to generally sum the usual effects of unilateral injection, producing effects of intermediate size. However, the absolute frequency change in any given site, or with any pair of sites, did not exceed 1 Hz, which is similar to what is seen with single injections in mSuM. Overall, it appears that at, any one time, theta frequency may be determined by a complex interplay between distinct but interacting modulatory regions in the medial hypothalamus.

Distinct patterns of neuronal inputs and outputs of the juxtaparaventricular and suprafornical regions of the lateral hypothalamic area in the male rat

“…In further support of this proposition, several hypothalamic sites have been identified for their responsiveness to stimulation of the rostral (oral) part of the pontine reticular nucleus (Vertes and Kocsis, 1997; Woodnorth et al, 2003), a brainstem site capable of eliciting the synchrony of hippocampal activity that is a necessary prerequisite for theta rhythm generation (Vertes, 1981; Vertes, 1982). Moreover, in addition to its classic association with locomotion in the rat (Vanderwolf, 1969), the hippocampal theta rhythm is also associated with other processes that may be predicted to have a bearing on defensive behavior.…”

Distribution of relaxin‐3 and RXFP3 within arousal, stress, affective, and cognitive circuits of mouse brain

“…Notably, very high densities of RLN3/RXFP3 were observed within the hippocampus and regions that regulate its function, including the medial septum/nucleus of the diagonal band, posterior hypothalamus, and supramammillary, interpeduncular, and median raphé nuclei, which together constitute the septohippocampal pathway (see e.g., Vertes, 1981;Vertes and Kocsis, 1997;Kirk, 1998;Pedemonte et al, 1998;Woodnorth et al, 2003;Woodnorth and McNaughton, 2005;Jackson et al, 2008). High levels of RLN3/RXFP3 were also observed in arousal-related brain areas, such as the raphé nuclei, lateral hypothalamus, and periaqueductal gray, while lower levels were present in other arousal structures, such as the ventral tegmental area and the pedunculopontine tegmental nucleus (see e.g., Mieda and Yanagisawa, 2002;Saper et al, 2005;Lu et al, 2006;Monti and Jantos, 2008).…”

Similar effects of medial supramammillary or systemic injection of chlordiazepoxide on both theta frequency and fixed-interval responding

“…Second, frequency is not determined solely by the mSuM in the awake rat, whereas it appears to be in the anesthetized preparation. Another nucleus or other nuclei must augment frequency control by the mSuM under normal behavioral conditions, and recent results from our laboratory suggest that the specific sites involved may vary according to conditions (Woodnorth, Kyd, Logan, Long, & McNaughton, 2002). Nonetheless, according to the view that theta frequency is important for hippocampal functioning,the mSuM would be expected to exert some influence over behaviors under hippocampal control.…”